Microbe Profile: Ruminococcus gnavus: the yin and yang of human gut symbionts

Graphical abstract


Graphical abstract Abstract
Ruminococcus gnavus is a human gut symbiont, part of the infant and adult gut microbiota and associated with intestinal and extra-intestinal disorders.R. gnavus mechanisms of adaptation to the gut are strain-specific and underpinned by the capacity of R. gnavus strains to utilize mucin and dietary glycans and produce bacteriocins and adhesins.Several potential mediators underpinning the association between R. gnavus strains and diseases have been identified, including the capacity to elicit a pro-or anti-inflammatory host response and modulate host metabolism, secondary bile acids and tryptophan metabolic pathways.Based on increasing evidence from metagenomics studies in humans and functional investigations in vitro and in mouse models, R. gnavus is emerging as a main player in influencing health and disease outcomes from infants to the elderly.

TAXONOMY AND PROPERTIES
Ruminococcus gnavus is a Gram-positive anaerobic bacterium belonging to the phylum Firmicutes, the class Clostridia and the cluster XIVa, and the family Lachnospiraceae.While retaining its full name from its original classification in the genus Ruminoccocus [1], R. gnavus has been temporarily classified into the genus Blautia and more recently into the genus Mediterraneibacter [2].The representative strain ATCC 29149 (=VPI C7-9) was isolated from human faeces.R. gnavus is generally regarded as a non-spore-former and strict anaerobe.R. gnavus end-fermentation products of carbohydrates include acetate, formate and ethanol, as well as propanol and propionate but not butyrate [3].

OCCURRENCE IN THE HUMAN GUT MICROBIOTA AND ASSOCIATION WITH HEALTH AND DISEASE
R. gnavus is a prevalent human gut symbiont and an early colonizer of the infant gut that persists throughout adulthood as 1 of 57 bacterial species present in more than 90 % of individuals with a median abundance of ~0.1 % across populations [4].R. gnavus belongs to the 24 'age-discriminatory' taxa whose changes in relative abundance over time are associated with normal 'maturation' of the microbiota and weight gain and metabolism in infants [5].
In addition of being a member of the 'normal' microbiota with beneficial properties, an increasing number of intraand extra-intestinal diseases have been associated with R. gnavus, as recently compiled [3], illustrating the yin and yang properties of R. gnavus strains.For example, a positive association has been reported with inflammatory bowel disease, including Crohn's disease, ulcerative colitis, irritable bowel syndrome or colon cancer, and with several features of metabolic syndromes in humans, with a consistently increased proportion of obesity, type 2 diabetes, liver and cardiovascular diseases.

KEY FEATURES AND PROPERTIES
The adaptation of R. gnavus to the gut is strain-dependent and associated with its capacity to utilize some human milk oligosaccharides and forage on mucin glycan epitopes, such as sialic acid (Neu5Ac), fucose, or blood group antigens in the mucus niche [3].Notably, R. gnavus ATCC 29149 has a unique sialic acid metabolic pathway dedicated to 2,7-anhydro-Neu5Ac [6].
There is a large degree of strain variation in R. gnavus functional properties.R. gnavus E1 produces several bacteriocins called ruminococcins that are active against pathogenic clostridia and multidrug-resistant strains [7].Several pro-inflammatory and anti-inflammatory factors have been identified in R. gnavus strains such as glucorhamnan and large capsular polysaccharides [8].This strain variation in the capacity of R. gnavus to elicit anti-or pro-inflammatory responses is reflected in a mouse model of diseases showing a beneficial or detrimental outcome of R. gnavus supplementation (as reviewed in [3]).At the molecular level, some R. gnavus strains display β-d-glucuronidase activity resulting in the removal of glucuronic acid from liver-produced β-d-glucuronides, while others produce an enzyme decarboxylating tryptophan into tryptamine [9] or 7β-hydroxysteroid dehydrogenases generating ursodeoxycholic acid from primary bile [10].R. gnavus tryptophan and bile acid metabolites have been implicated in the role of R. gnavus in inflammation and metabolic disorders, but also the development of neuro/psychological disorders [11], although causality remains to be demonstrated.

OPEN QUESTIONS
Does the capacity of R. gnavus strains to utilize different carbohydrates in vitro reflect ecological niches in the gut?What is the spatial distribution of R. gnavus strains in the infant and adult gastrointestinal tract?Which R. gnavus strains/niches are associated with specific diseases?Can we rationally design nutritional interventions that target particular R. gnavus niche-associated strains?Which R. gnavus functional properties play a causal role in health or diseases?Can microbial-based approaches such as phage therapy can be used to reduce overgrowth of R. gnavus strains associated with diseases while preserving R. gnavus associated with host health benefits?